Background: NIVO, a programmed death-1 immune checkpoint inhibitor, improved response rates and progression-free survival (PFS) compared with chemotherapy in MEL patients (pts) who progressed after IPI in the phase III CheckMate 037 trial (Lancet Oncol 2015;16:375). We assessed NIVO monotherapy in pts with MEL who had progressed on or after IPI, including pts with poor prognostic factors who have been largely excluded from clinical trials (eg, ECOG performance status [PS] 2, brain metastases). Methods: In this ongoing phase II, single-arm, open-label, multicenter study, European pts with MEL who progressed on or after IPI are treated with NIVO 3 mg/kg Q2W for up to 2 years until progression or unacceptable toxicity (NCT02156804). The primary endpoint is safety; secondary endpoints include objective response rate (ORR). We report safety in the first 307 treated pts (database lock, November 2015; minimum follow-up of 6 months). Results: At baseline, 8% of pts had ECOG PS 2, 65% had M1c disease, 15% had a history of brain metastases, and 29% had received ≥ 3 prior therapies. Overall, 256 (84%) patients received at least 4 doses of NIVO, while 241 (79%) received > 4 doses. The incidence of treatment-related any grade and grade 3/4 adverse events (AEs) were 58% and 11%, respectively. Discontinuations due to treatment-related AEs occurred in 3% of pts. No treatment-related deaths were reported. The most common treatment-related select AEs (ie, potentially immune-related) were dermatologic (19%), endocrine (9%), gastrointestinal (7%), and hepatic (5%). ORR data are planned to be available for the presentation. Conclusions: CheckMate 172 represents the largest study of NIVO safety and efficacy in pts with MEL who progressed on or after IPI. In this initial report, NIVO demonstrated a safety profile consistent with previously reported clinical trial data. Clinical trial information: NCT02156804